Gene expression analysis of major lineage-defining factors in human bone marrow cells: Effect of aging, gender, and age-related disorders
Gene expression analysis of major lineage-defining factors in human bone marrow cells: Effect of aging, gender, and age-related disorders
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DOI：
10.1002/jor.20623
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发表时间：
2008-07-01
影响因子：
2.8
通讯作者：
Uemura, Toshimasa
中科院分区：
文献类型：
--
作者：
Jiang, Ying;Mishima, Hajime;Uemura, Toshimasa
成体骨髓细胞（BMCs）包括两个群体：间充质干细胞（MSCs），其可以分化成骨、软骨和脂肪;和造血干细胞（HSCs），其产生所有成熟的血液谱系。为了研究年龄、性别和年龄相关疾病对谱系分化的影响，我们采用定量RT-PCR检测了80名健康受试者和患者骨髓中定义BMC谱系的主要因子（成骨细胞cbfa 1、脂肪细胞ppar-gamma、软骨细胞sox 9和破骨细胞rank 1）的mRNA表达（14-79岁），患有两种年龄相关疾病：骨关节炎（OA）和类风湿性关节炎（RA）。研究了两个凋亡相关基因bcl-2和drak 1。RANKL和PPAR-Gamma水平在女性患者中与年龄呈明显正相关，但在男性患者中则不然，CBFa 1转录物呈轻微的年龄相关性下降。DRAK 1表达显示出与年龄相关的上升趋势，女性中RANKL和DRAK 1的转录物显著更高（p < 0.01）。与年龄匹配的对照组相比，RA患者显示RANKL、PPAR-Gamma和DRAK 1 mRNA水平升高（p < 0.05），OA患者显示RANKL和PPAR-Gamma转录水平升高（p < 0.05）。RA组中SOX 9和DRAK 1的表达高于OA组（p < 0.05）。我们的数据表明，衰老和年龄相关的疾病影响基因的表达不同，这表明在衰老，骨髓细胞的谱系被修改的显着变化，减少骨髓成骨细胞，增加脂肪和破骨细胞，而在年龄相关的疾病，骨髓脂肪和破骨细胞的活性或数量可能在关节炎性骨丢失的发病机制中发挥重要作用。(C)2008骨科研究学会。由威利期刊公司出版
Adult bone marrow cells (BMCs) include two populations:; mesenchymal stem cells (MSCs), which can differentiate into bone, cartilage, and fat; and hematopoietic stem cells (HSCs), which produce all mature blood lineage. To study the effect of aging, gender, and age-related disorders on lineage differentiation, we performed quantitative RT-PCR to examine mRNA expression of the major factors defining BMC lineage, cbfa1 for osteoblasts, ppar-gamma for adipocytes, sox9 for chondrocytes, and rank1 for osteoclasts, in bone marrow from 80 healthy subjects and patients (14-79 years old) with two age-related disorders: osteoarthritis (OA) and rheumatoid arthritis (RA). Two apoptosis-related genes, bcl-2 and drak1, were studied. RANKL and PPAR-Gamma levels exhibited a clear positive correlation with age in female patients, but not in males, with a slight age-related decline in CBFa1 transcripts. DRAK1 expression showed an age-associated ascending trend with significantly greater transcripts of RANKL and DRAK1 in females (p < 0.01). Compared with age-matched controls, RA patients exhibited increased RANKL, PPAR-Gamma, and DRAK1 mRNA levels (p < 0.05), and OA showed the higher RANKL and PPAR-Gamma transcripts (p < 0.05). Furthermore, SOX9 and DRAK1 expressions in the RA group were higher than in the OA group (p < 0.05). Our data indicate that aging and age-related disorders affect gene expressions differently, suggesting that in aging, the lineage of bone marrow cells was modified with prominent changes in decreased bone marrow osteoblastogenesis, increased adipogenesis and osteoclastogenesis, while in age-related disorders, marrow adipogenesis and the activity or number of osteoclasts may play an important role in the pathogenesis of arthritic bone loss. (C) 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.